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Coronary artery disease (CAD) has become one of the leading causes of death worldwide.Percutaneous coronary intervention (PCI) is one of the main treatments for CAD. Coronary in-stent restenosis(ISR) refers to the re-narrowing of the artery following PCI, occurring in approximately 10% of cases. Coronary ISR is a highly complex condition, and while its exact pathogenesis remains unclear, it is widely believed to involve processes such as inflammation, proliferation and stromal vascular remodeling. Several risk factors have been identified as being associated with coronary ISR, including inflammation, genetic predisposition, plaque heterogeneity, and improper stent placement during PCI. These factors not only help categorize patient risk but also deepen our understanding of coronary ISR,aiding in the development of individualized treatment plans.Over the past four decades, numerous new materials and techniques have been employed to prevent and treat coronary ISR, including drug eluting stents, innovative pharmacotherapies, advanced intravascular imaging techniques,biodegradable stents, as well as cell and gene therapies. Despite these advancements, coronary ISR remains a significant PCI complication. Thus, recognizing the risk factors, understanding the pathogenic mechanisms, and exploring new treatment strategies for coronary ISR are critical. This article aims to review the latest advancements in the risk factors, pathogenic mechanisms, and treatment of coronary ISR, providing reference for clinicians and future researchers.

ObjectivesLevofloxacin is widely used because of its broad-spectrum antimicrobial activity and convenient dosing schedule. However, the relevance of its use in children remains to be investigated. The purpose of this study is to investigate the efficacy and safety of levofloxacin use in children with severe infections.MethodsWe conducted a retrospective observational study of patients

N6-methyladenosine (M6A) is the most common modification in eukaryotic RNAs for the regulation of RNA transcription, processing, splicing, degradation, and translation. RNA modification by M6A is dynamically reversible, involving methylated transferase, demethylase, and methylated reading protein. M6A-mediated gene regulation involves cell differentiation, metastasis, apoptosis, and proliferation. Dysregulation of M6A can lead to various diseases. Cardiovascular disease (CVD) seriously endangers human health and brings great social burden. Seeking effective prevention and treatment strategies for CVD is a challenge to both fundamentalists and clinicians. Substantial evidence has suggested the key role of M6A modification in the development of CVDs. This review summarizes the mechanism of M6A RNA modification and the latest research progress in respect with its role in CVDs, including atherosclerosis, coronary artery disease, myocardial infarction and cardiac remodeling, myocardial ischemia-reperfusion injury, heart failure, hypertension, and aortic aneurysm, and the potential applications of the findings to CVDs, thereby providing new ideas and approaches for the diagnosis and therapy of CVDs.

The excessive discharge of antibiotics into aquatic systems is a major issue in many countries worldwide and poses a threat to human health and the sustainable development of society. Hence, developing efficient treatment methods and purification technologies to degrade antibiotics is essential. Herein, we present the synthesis of low-cost, self-propelled tubular Fe3+-incorporated graphitic carbon nitride (g-C3N4-Fe@KF) micromotors using kapok fibers (KFs) as templates and their application as photo-catalysts for the photo-Fenton degradation of tetracycline (TC) under visible-light irradiation. The g-C3N4-Fe@KF micromotors moved rapidly when being propelled by oxygen bubbles generated in a hydrogen peroxide (H2O2) solution as a result of a photo-assisted Fenton reaction. The motion behavior of the g-C3N4-Fe@KF micromotors was dependent on the concentration of H2O2 and the length of the micromotors. The propulsion mechanism was discussed in detail. The micromotors efficiently degraded antibiotics via the photo-Fenton process. Photo-Fenton degradation efficiency was attributed to the synergistic effects of the doped Fe3+ and g-C3N4 under visible-light irradiation and self-propulsion of the micromotors. In addition, the micromotors possessed good reusability, thereby efficiently realizing multiple cycles of degradation. The current work offers an avenue for the design of micromotors, using inexpensive approaches, for various potential environmental applications. [ABSTRACT FROM AUTHOR]

Epsilon toxin (ETX), a potential agent of biological and toxic warfare, causes the death of many ruminants and threatens human health. It is crucial to understand the toxic mechanism of such a highly lethal and rapid course toxin. In this study, we detected the effects of ETX on the proteome and phosphoproteome of MDCK cells after 10 min and 30 min. A total of 44 differentially expressed proteins (DEPs) and 588 differentially phosphorylated proteins (DPPs) were screened in the 10 min group, while 73 DEPs and 489 DPPs were screened in the 30 min group. ETX-induced proteins and phosphorylated proteins were mainly located in the nucleus, cytoplasm, and mitochondria, and their enrichment pathways were related to transcription and translation, virus infection, and intercellular junction. Meanwhile, the protein–protein interaction network screened out several hub proteins, including SRSF1/2/6/7/11, SF3B1/2, NOP14/56, ANLN, GTPBP4, THOC2, and RRP1B. Almost all of these proteins were present in the spliceosome pathway, indicating that the spliceosome pathway is involved in ETX-induced cell death. Next, we used RNAi lentiviruses and inhibitors of several key proteins to verify whether these proteins play a critical role. The results confirmed that SRSF1, SF3B2, and THOC2 were the key proteins involved in the cytotoxic effect of ETX. In addition, we found that the common upstream kinase of these key proteins was SRPK1, and a reduction in the level of SRPK1 could also reduce ETX-induced cell death. This result was consistent with the phosphorylated proteomics analysis. In summary, our study demonstrated that ETX induces phosphorylation of SRSF1, SF3B2, THOC2, and SRPK1 proteins on the spliceosome pathway, which inhibits normal splicing of mRNA and leads to cell death. [ABSTRACT FROM AUTHOR]

Nano‐delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral‐mimicking ternary polyplexes system for the controlled delivery of the anti‐inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44‐mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral‐mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral‐mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have certain effect in cancer treatment, thus many studies have been focused on developing functional systems to generate ROS in tumor. Here, inspired by the multi‐enzyme biocatalysis in organisms, novel ultrasound‐triggered temporospatial catalytic cascades systems are presented based on barium titanate (BTO) and platinum (Pt) co‐loaded multi‐component microparticles (Pt/BTO@MCMPs) to successively achieve oxygen and ROS production for tumor sonodynamic therapy. By using a customized capillary microfluidic device, the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part, alternating with blank porous hydrogel components for increasing interaction areas between the encapsulated nanomaterials and the ambient substrates. In the microparticles, the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions, contributing to additional generation of ROS under US activation. Based on the system, it is demonstrated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors. These results indicate that the proposed ultrasound‐triggered temporospatial catalytic cascades systems are promising for clinic anti‐tumor applications. [ABSTRACT FROM AUTHOR]

IntroductionTherapeutic drug monitoring (TDM) has been shown to be clinically beneficial for critically ill patients. However, this is a burden for neonates or children with small circulating blood volumes. Here, we aimed to develop and validate a microsampling TDM platform (including dried blood spots (DBS) and capillary microsamples (CMS)) for the simultaneous quantification of vancomycin, meropenem, and linezolid.MethodsPaired DBS and CMS samples were obtained from an intensive care unit (ICU) to evaluate its clinical application. Estimated plasma concentrations (EPC) were calculated from DBS concentrations. Agreement between methods was evaluated using Deming regression and Bland-Altman difference plots.ResultsThe microsampling methods validation showed excellent reliability and compatibility with the analysis of the sample matrix and hematocrit range of the studied population. The DBS and CMS accuracy and precision results were within accepted ranges and samples were stable at room temperature for at least 2 days and 8 h, respectively. Hematocrit had no impact on CMS, but sightly impacted DBS measurements. The CMS and DBS antibiotic concentrations correlated well (r > 0.98). The drug concentration ratio in DBS samples to that in CMS was 1.39 for vancomycin, 1.34 for meropenem, and 0.94 for linezolid. The EPC calculated from the DBS using individual hematocrit ranges presented comparable absolute values for vancomycin (slope: 1.06) and meropenem (slope: 1.04), with a mean of 98% and 99% of the measured CMS concentrations, respectively.DiscussionThis study provides a microsampling TDM platform validated for clinical use for a rapid quantification of three antibiotics and is suitable for real-time TDM-guided personalization of antimicrobial treatment in critically ill children.